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Bipolar DisorderPhase 3NCT02670538

Study of the Efficacy of a Fixed-dose Regimen of Cariprazine Compared to Placebo for Treatment of the Depressive Episode in Participants With Bipolar I Disorder

A Phase 3 study testing Cariprazine in people with Bipolar Disorder and Depression, run by Forest Laboratories at 89 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study is designed to prospectively confirm the efficacy of a fixed-dose regimen of cariprazine 1.5 milligrams (mg)/day or 3 mg/day compared to placebo for treatment of the depressive episode in participants with bipolar I disorder. The safety and tolerability of the fixed-dose regimens will be evaluated. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Bipolar Disorder, Depression
What is being tested?
Cariprazine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
493 participants
Where
89 sitesin 8 countries
Study dates
31 Mar 2016to 18 Jan 2018
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Currently meet the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for bipolar I disorder without psychotic features confirmed by the administration of the Mini International Neuropsychiatric Interview (MINI), with a current major depressive episode of at least 4 weeks and not exceeding 12 months in duration
  • Currently treated as an outpatient at the time of enrollment
  • A verified previous manic or mixed episode. Verification must include one of the following sources:
  • Treatment of mania with an anti-manic agent (eg, lithium or divalproate) or antipsychotic medication with an approved indication for mania
  • Hospital records/Medical records
  • Patient report corroborated by caretaker or previous or current treating clinician
Show all 11Show fewer
  • 17-item Hamilton Depression Rating Scale (HAMD-17) total score ≥ 20
  • HAMD-17 item 1 score ≥ 2
  • CGI-S score ≥ 4
  • Negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test (women of childbearing potential only)
  • Normal physical examination, clinical laboratory test results, and electrocardiogram (ECG) results or abnormal findings that are judged not clinically significant by the Principal Investigator (PI)

Who cannot join

  • Young Mania Rating Scale (YMRS) total score > 12
  • Four or more episodes of a mood disturbance (depression, mania, hypomania, or mixed state) within the 12 months before Visit 1
  • Any current axis 1 psychiatric diagnosis other than bipolar disorder with the exception of specific phobias
  • History of meeting DSM-5 criteria for:
  • Dementia, amnesic, or other cognitive disorder
  • Schizophrenia, schizoaffective, or other psychotic disorder
Show all 25Show fewer
  • Mental retardation
  • DSM-5-based diagnosis of borderline or antisocial personality disorder or other axis II disorder of sufficient severity to interfere with participation in this study
  • History of meeting DSM-5 criteria for alcohol or substance abuse or dependence (other than nicotine or caffeine) within the 6 months before Visit 1
  • Positive result on blood alcohol test or urine drug screen for any prohibited medication. Exception:
  • Patients with a positive cannabinoid on entry may be retested before randomization. If the patient remains positive, the patient is no longer eligible
  • Patients positive for opiates on entry, discussion with Study Physician is required.
  • Electroconvulsive therapy in the 3 months before Visit 1
  • Previous lack of response to electroconvulsive therapy
  • Treatment with a depot antipsychotic drug within 1 treatment cycle before Visit 1
  • Treatment with clozapine in a dose of > 50 mg/day in the past 2 years
  • Prior participation in any investigational study of RGH-188 or cariprazine within the past 12 months
  • Previous treatment with vagus nerve stimulation or transcranial magnetic stimulation within 6 months before Visit 1
  • Prior participation with any clinical trials, involving experimental or investigational drugs, within 6 months before Visit 1 or during the study
  • Initiation or termination of psychotherapy for depression within the 3 months preceding Visit 1, or plans to initiate, terminate, or change such therapy during the course of the study.
  • Pregnant, breastfeeding, or planning to become pregnant or breastfeed during the study
  • Gastric bypass or any condition that would be expected to affect drug absorption (lap band procedures are acceptable if there is no problem with absorption)
  • Known history of cataracts or retinal detachment
  • Known human immunodeficiency virus infection
  • Employee, or immediate relative of an employee, of the Sponsor, any of its affiliates or partners, or the study center

Trial locations and contacts

89 sites in 8 countries.

89 sites in 8 countries

United States42 sites

  • Advanced Research Center, Inc

    Anaheim, California, 92805

  • Atlanta Center for Medical Research

    Atlanta, Georgia, 30331

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Pacific Institute of Medical Sciences

    Bothell, Washington, 98011

  • Brooklyn Medical Institute

    Brooklyn, New York, 11214

  • SPRI Clinical Trials, LLC

    Brooklyn, New York, 11235

  • University at Buffalo Erie County Medical Center

    Buffalo, New York, 14215

  • Radiant Research

    Cerritos, California, 90703

  • Carolina Clinical Trials, Inc.

    Charleston, South Carolina, 29407

  • Center for Emotional Fitness

    Cherry Hill, New Jersey, 08002

  • University of Cincinnati - Department of Psychiatry and Behavioral Neuroscience

    Cincinnati, Ohio, 45219

  • CNS Clinical Research Group

    Coral Springs, Florida, 33067

  • Millennium Psychiatric Associates

    Creve Coeur, Missouri, 63141

  • Harmonex Neuroscience Research, Inc.

    Dothan, Alabama, 36303

  • Collaborative Neuroscience Network, LLC

    Garden Grove, California, 92845

  • Behavioral Research Specialists, LLC

    Glendale, California, 91206

  • MD Clinical

    Hallandale, Florida, 33009

  • Clinical Trials of America, Inc

    Hickory, North Carolina, 28601

  • Alexian Brothers Center for Psychiatric Research

    Hoffman Estates, Illinois, 60169

  • Houston Endoscopy and Research Center

    Houston, Texas, 77079

  • Innovative Clinical Research, Inc.

    Lauderhill, Florida, 33319

  • Capstone Clinical Research

    Libertyville, Illinois, 60048

  • Woodland International Research Group, LLC

    Little Rock, Arkansas, 72211

  • Pharmaceutical Research Associates, Inc.

    Marlton, New Jersey, 08053

  • Professional Psychiatric Services

    Mason, Ohio, 45040

  • Suburban Research Associates

    Media, Pennsylvania, 19063

  • Innova Clinical Trials, Inc.

    Miami, Florida, 33133

  • Baber Research Group

    Naperville, Illinois, 60563

  • Manhattan Behavioral Medicine

    New York, New York, 10036

  • Eastside Comprehensive Medical Center

    New York, New York, 10128

  • Research Centers of America, LLC

    Oakland Park, Florida, 33334

  • Excell Research, Inc.

    Oceanside, California, 92056

  • Cutting Edge Research Group

    Oklahoma City, Oklahoma, 73116

  • NoesisPharma, LLC

    Phoenix, Arizona, 85032

  • Finger Lakes Clinical Research

    Rochester, New York, 14618

  • J. Gary Booker, MD, APMC

    Shreveport, Louisiana, 71104

  • St. Louis Clinical Trials, LLC

    St Louis, Missouri, 63141

  • Collaborative Neuroscience Network, LLC

    Torrance, California, 90502

  • Tulsa Clinical Research, LLC

    Tulsa, Oklahoma, 74104

  • Comprehensive Clinical Research

    Washington D.C., District of Columbia, 20016

  • Coastal Research Associates, Inc.

    Weymouth, Massachusetts, 02190

  • Grayline Research Center

    Wichita Falls, Texas, 76309

Other trials in United States

Ukraine12 sites

  • CI of Kyiv Reg.Council Reg.Psychiatric-Narcological Medical Association

    Hlevakha, 08631

  • Regional Psychoneurological Hospital #3, Dept of Primary Psych Episode

    Ivano-Frankivsk, 76014

  • Regional Psychoneurological Hospital #3

    Ivano-Frankivsk, 76014

  • SI Inst.of Neurology, Psychiatry and Narcology of NAMS of Ukraine

    Kharkiv, 61068

  • CI Kherson Reg. Psychiatric Hospital of Kherson RC

    Kherson, 73488

  • CI Odesa Regional Psychiatric Hospital # 2

    Komintern, 67513

  • CI of LRC Lviv Reg. Council Lviv Reg.Clinical Psychoneurological Dispensary

    Lviv, 79017

  • CI Odesa Regional Medical Center of Mental Health

    Odesa, 65006

  • CI Cherkasy Regional Psychiatric Hospital of ChRC

    Smila, 20708

  • Ternopil Reg. Communal Clinical Psychoneurological Hospital Depts of Psychiatry #2

    Ternopil, 46027

  • Transcarpathian Regional Narcological Dispensary

    Uzhhorod, 88000

  • CI O.I. Yushchenko Vinnytsia Reg. Psychoneurological Hospital

    Vinnytsia, 21005

Other trials in Ukraine

Serbia11 sites

  • Clinic of Psychiatric Diseases "Dr Laza Lazarevic"

    Belgrade, 11000

  • Clinical Center of Serbia

    Belgrade, 11000

  • Clinical Center Zvezdara

    Belgrade, 11000

  • General Hospital Euromedic

    Belgrade, 11000

  • Institute of Mental Health

    Belgrade, 11000

  • Clinical Center "Dr. Dragisa Misovic"

    Belgrade, 11040

  • Clinical Center Kragujevac Site 154

    Kragujevac, 34000

  • Clinical Centre Kragujevac Site 158

    Kragujevac, 34000

  • Clinical Center Nis Site 150

    Niš, 18000

  • Clinical Center Nis Site 160

    Niš, 18000

  • Specialized Hospital for Neuropsychiatric Diseases "Sveti Vracevi"

    Novi Kneževac, 23330

Other trials in Serbia

Bulgaria6 sites

  • Mental Health Centre 'Prof. Dr. Ivan Temkov', EOOD

    Burgas, 8001

  • MHAT "Dr. Hristo Stambolski", EOOD

    Kazanlak, 6100

  • UMHAT 'Dr. Georgi Stranski', Dept. of Psychiatry

    Pleven, 5800

  • UMHAT "Sv. Georgi", EAD

    Plovdiv, 4000

  • DCC "Mladost M" - Varna, OOD Site 188

    Varna, 9020

  • DCC "Mladost M" - Varna, OOD Site 194

    Varna, 9020

Other trials in Bulgaria

Croatia6 sites

  • Neuropsychiatric Hospital Ivan Barbot

    Popovača, 44317

  • Clinical Hospital Center Rijeka

    Rijeka, 51000

  • Polyclinic Neuron

    Zagreb, 10000

  • University Hospital Center Zagreb

    Zagreb, 10000

  • Clinic for Psychiatry Vrapce

    Zagreb, 10090

  • Psychiatric Hospital "Sveti Ivan"

    Zagreb, 10090

Other trials in Croatia

Slovakia6 sites

  • Centrum zdravia R.B.K. s.r.o.

    Bardejov, 08501

  • Vavrusova Consulting s.r.o.

    Bratislava, 85101

  • Liptovska nemocnica s poliklinikou Liptovsky Mikulas

    Liptovský Mikuláš, 03123

  • PsychoLine s.r.o.

    Rimavská Sobota, 97901

  • Nemocnica s poliklinikou sv. Barbory, Roznava a.s.

    Rožňava, 04801

  • Crystal Comfort s.r.o.

    Vranov nad Topľou, 09301

Other trials in Slovakia

Romania5 sites

  • Spitalul Universitar de Urgenta Militar Central "Dr. Carol Davila"

    Bucharest, 010825

  • Spitalul de Psihiatrie Titan "Dr. Constantin Gorgos"

    Bucharest, 030442

  • Spitalul de Psihiatrie "Elisabeta Doamna" Galati

    Galati, 800179

  • Institutul de Psihiatrie Socola Iasi Site 111

    Iași, 700282

  • Institutul de Psihiatrie Socola Iasi Site 113

    Iași, 700282

Other trials in Romania

Puerto Rico1 site

  • Barbara Diaz-Hernandez MD Research, Inc.

    San Juan, 00926

Other trials in Puerto Rico

About this study

Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter, Fixed-Dose Clinical Trial Evaluating The Efficacy, Safety And Tolerability Of Cariprazine In Patients With Bipolar I Depression

This study is designed to prospectively confirm the efficacy of a fixed-dose regimen of cariprazine 1.5 milligrams (mg)/day or 3 mg/day compared to placebo for treatment of the depressive episode in participants with bipolar I disorder. The safety and tolerability of the fixed-dose regimens will be evaluated.

Being tested
Cariprazine, Placebo
Medical subject headings
Bipolar Disorder, Depression

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CariprazineDrug

    Also called Vraylar

    Cariprazine capsule one per day orally.

  • PlaceboDrug

    Matching placebo capsule one per day orally.

Study groups in NCT02670538
Study groupRoleWhat they receive
Cariprazine 3.0 mgExperimentalFollowing a 7 to 14 days screening/washout period, cariprazine 1.5 milligrams (mg) capsule, one per day, orally for 2 weeks increased to cariprazine 3.0 mg capsule, one per day orally beginning on Day 15 for 4 weeks.
Receives: Drug: Cariprazine
Cariprazine 1.5 mgExperimentalFollowing a 7 to 14 days screening/washout period, cariprazine 1.5 mg capsule, one per day, orally for 6 weeks.
Receives: Drug: Cariprazine
PlaceboPlacebo comparatorFollowing a 7 to 14 days screening/washout period, matching placebo capsule, one per day, orally for 6 weeks.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS)

    MADRS is a 10-item, clinician-rated scale that evaluates the participants depressive symptomatology during the past week. Participants were rated on items assessing feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty in concentration, and lack of interest. Each of the 10 items was scored on a 7-point scale with a score of 0 reflecting no symptoms and a score of 6 reflecting symptoms of maximum severity for a total possible score of 0 (best) to 60 (worst). A negative change from Baseline indicates improvement. Mixed-effects Model for Repeated Measures (MMRM) with fixed factors (treatment group, pooled study center, and visit), baseline (a covariate), and interactions (treatment group by visit, baseline by visit).

    Measured: Baseline (Week 0) to Week 6

Secondary outcomes (1)

  1. Change From Baseline in Clinical Global Impressions-Severity (CGI-S) Score

    CGI-S is a clinician-rated scale that measures the overall severity of a participant's illness in comparison with the severity of other patients the physician has observed. The participant was rated on a scale from 1 to 7, with 1 indicating a "normal state" and 7 indicating "among the most extremely ill patients". A negative change from Baseline indicates improvement. MMRM with fixed factors (treatment group, pooled study center, and visit), baseline (a covariate), and interactions (treatment group by visit, baseline by visit).

    Measured: Baseline (Week 0) to Week 6

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Feb 2016 (estimated)
  2. Study start31 Mar 2016
  3. Primary completion18 Jan 2018
  4. Study completion18 Jan 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
493 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02670538
Sponsor's protocol ID
RGH-MD-53
Other IDs
2016-000756-98, 2016
Status last verified
Feb 2019
First submitted
28 Jan 2016
Last updated
12 Mar 2019
Data monitoring committee
No

Publications

  • McIntyre RS, Llorca PM, Aronin LC, Yu J, Nguyen HB. Effect of Cariprazine on Anhedonia in Patients with Bipolar I Depression: Post Hoc Analysis of Three Randomized Placebo-Controlled Clinical Trials. Adv Ther. 2025 Jan;42(1):246-260. doi: 10.1007/s12325-024-03009-2. Epub 2024 Nov 9.

    PubMed 39520655

  • Jain R, McIntyre RS, Cutler AJ, Earley WR, Nguyen HB, Adams JL, Yatham LN. Efficacy of cariprazine in patients with bipolar depression and higher or lower levels of baseline anxiety: a pooled post hoc analysis. Int Clin Psychopharmacol. 2024 Mar 1;39(2):82-92. doi: 10.1097/YIC.0000000000000500. Epub 2023 Sep 20.

    PubMed 37551609

  • Citrome L, Yatham LN, Patel MD, Barabassy A, Hankinson A, Earley WR. Cariprazine and akathisia, restlessness, and extrapyramidal symptoms in patients with bipolar depression. J Affect Disord. 2021 Jun 1;288:191-198. doi: 10.1016/j.jad.2021.03.076. Epub 2021 Mar 31.

    PubMed 33915374

  • Thase ME, Harrington A, Calabrese J, Montgomery S, Niu X, Patel MD. Evaluation of MADRS severity thresholds in patients with bipolar depression. J Affect Disord. 2021 May 1;286:58-63. doi: 10.1016/j.jad.2021.02.043. Epub 2021 Feb 20.

    PubMed 33677183

  • Yatham LN, Vieta E, McIntyre RS, Jain R, Patel M, Earley W. Broad Efficacy of Cariprazine on Depressive Symptoms in Bipolar Disorder and the Clinical Implications. Prim Care Companion CNS Disord. 2020 Sep 17;22(5):20m02611. doi: 10.4088/PCC.20m02611.

    PubMed 32942346

  • Earley WR, Burgess M, Rekeda L, Hankinson A, McIntyre RS, Suppes T, Calabrese JR, Yatham LN. A pooled post hoc analysis evaluating the safety and tolerability of cariprazine in bipolar depression. J Affect Disord. 2020 Feb 15;263:386-395. doi: 10.1016/j.jad.2019.11.098. Epub 2019 Nov 22.

    PubMed 31969269

  • Earley WR, Burgess MV, Khan B, Rekeda L, Suppes T, Tohen M, Calabrese JR. Efficacy and safety of cariprazine in bipolar I depression: A double-blind, placebo-controlled phase 3 study. Bipolar Disord. 2020 Jun;22(4):372-384. doi: 10.1111/bdi.12852. Epub 2019 Nov 6.

    PubMed 31628698

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Cariprazine in people with Bipolar Disorder and Depression, run by Forest Laboratories at 89 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 89 sites in United States, Ukraine, Serbia, Bulgaria, Croatia and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) (time frame: Baseline (Week 0) to Week 6). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02670538, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Mar 2019; AzTrials last refreshed its copy on 7 Nov 2026.

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